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OBJECTIVE: There is paucity of information about status epilepticus (SE) in tuberculous meningitis (TBM). In this communication, we report SE semiology, response to antiseizure medication (ASM) and outcome of the TBM patients with SE. METHODS: The diagnosis of TBM was based on clinical, cerebrospinal fluid and MRI findings. The clinical details, severity of meningitis, and MRI and electroencephalography findings were noted. The type of SE, onset from the meningitis symptoms, number of ASMs required to control SE and outcomes were noted. RESULTS: During study period from august 2015 to march 2023, 143 TBM patients were admitted and 10 (6.9 %) had SE, whose age ranged between 12 and 45 years. MRI revealed exudates in six, hydrocephalus in three, infarctions in seven and tuberculoma in six patients. Median (interquartile range) duration of SE after meningitis symptoms was 65 (43.7-100.5) days. Three had generalized convulsive SE, three epileptia partialis continua (EPC), three focal convulsive SE with bilateral convulsion, and one had non-convulsive SE. Two (20 %) patients responded to two ASMs, six (60 %) had refractory SE whose seizure continued after benzodiazepine and one ASM, and two (20 %) had super-refractory SE having seizures for ≥ 24 h despite use of intravenous anesthetic agent. Four (40 %) patients died; uncontrolled SE resulted death in one, and the remaining patients died due to primary disease. Only 2 (20 %) patients had good recovery and 4 (40 %) had poor recovery at 6 months. CONCLUSION: Status epilepticus in TBM is uncommon and can be refractory or super-refractory resulting in poor outcome.
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OBJECTIVE: Super-refractory status epilepticus (SRSE) is an enduring or recurring SE after 24 h or more of general anesthesia. This study aimed to evaluate the efficacy and safety of phenobarbital (PB) for the treatment of SRSE. METHODS: This retrospective, multicenter study included neurointensive care unit (NICU) patients with SRSE treated with PB between September 2015 and September 2020 from six participating centers of the Initiative of German NeuroIntensive Trial Engagement (IGNITE) to evaluate the efficacy and safety of PB treatment for SRSE. The primary outcome measure was seizure termination. In addition, we evaluated maximum reached serum levels, treatment duration, and clinical complications using a multivariate generalized linear model. RESULTS: Ninety-one patients were included (45.1% female). Seizure termination was achieved in 54 patients (59.3%). Increasing serum levels of PB were associated with successful seizure control (per µg/mL: adjusted odds ratio [adj.OR] = 1.1, 95% confidence interval [CI] 1.0-1.2, p < .01). The median length of treatment in the NICU was 33.7 [23.2-56.6] days across groups. Clinical complications occurred in 89% (n = 81) of patients and included ICU-acquired infections, hypotension requiring catecholamine therapy, and anaphylactic shock. There was no association between clinical complications and treatment outcome or in-hospital mortality. The overall average modified Rankin scale (mRS) at discharge from the NICU was 5 ± 1. Six patients (6.6%) reached mRS ≤3, of whom five were successfully treated with PB. In-hospital mortality was significantly higher in patients in whom seizure control could not be achieved. SIGNIFICANCE: We observed a high rate in attainment of seizure control in patients treated with PB. Success of treatment correlated with higher dosing and serum levels. However, as one would expect in a cohort of critically ill patients with prolonged NICU treatment, the rate of favorable clinical outcome at discharge from the NICU remained extremely low. Further prospective studies evaluating long-term clinical outcome of PB treatment as well as an earlier use of PB at higher doses would be of value.
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Estado Epiléptico , Humanos , Feminino , Masculino , Estudos Retrospectivos , Estudos Prospectivos , Estado Epiléptico/terapia , Fenobarbital/uso terapêutico , Convulsões/tratamento farmacológico , Mortalidade HospitalarRESUMO
Status epilepticus (SE) is a neurological emergency characterized by high rates of short-term and long-term morbidity and mortality. Status epilepticus seems to be a marker of the severity of other underlying conditions rather than a determinant of death on its own. Careful diagnosis and acute treatment of complications and causes of death to SE or its underlying etiology will enable the differentiation of SE patients that would benefit from different levels of treatment intensity. All SE patients should be treated actively with first- and second-line drugs as early as possible. For cases in which seizures continue after second-line treatment, the current guidelines fail to offer possibilities other than the active path with general anesthesia and intensive care unit (ICU) care. However, the intensity of care should be evaluated before starting ICU care or in unclear cases with the time-limited trial at ICU. There are now multiple possibilities for specialty palliative SE care that include sequential and add-on use of second-line drugs and palliative sedation at the ward. If ICU care is prolonged, the patient's status needs to be constantly re-evaluated and communicated to the family. When patients exhibit multiple predictors of mortality and poor functional outcomes, they should be allowed to have a natural death in a peaceful environment without unnecessarily prolonged suffering. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.
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Estado Epiléptico , Assistência Terminal , Humanos , Estado Epiléptico/terapia , Estado Epiléptico/tratamento farmacológico , Convulsões/diagnóstico , Cuidados Paliativos , Unidades de Terapia Intensiva , Anticonvulsivantes/uso terapêuticoRESUMO
BACKGROUND AND OBJECTIVES: Clinicians have treated super refractory status epilepticus (SRSE) with electroconvulsive therapy (ECT); however, data supporting the practice are scant and lack rigorous evaluation of continuous electroencephalogram (cEEG) changes related to therapy. This study aims to describe a series of patients with SRSE treated at our institution with ECT and characterize cEEG changes using a blinded review process. METHODS: We performed a single-center retrospective study of consecutive patients admitted for SRSE and treated with ECT from January 2014 to December 2022. Our primary outcome was the resolution of SRSE. Secondary outcomes included changes in ictal-interictal EEG patterns, anesthetic burden, treatment-associated adverse events, and changes in clinical examination. cEEG was reviewed pre- and post-ECT by blinded epileptologists. RESULTS: Ten patients underwent treatment with ECT across 11 admissions (8 female, median age 57 years). At the time of ECT initiation, nine patients had ongoing SRSE while two had highly ictal patterns and persistent encephalopathy following anesthetic wean, consistent with late-stage SRSE. Super-refractory status epilepticus resolution occurred with a median time to cessation of 4 days (interquartile range [IQR]: 3-9 days) following ECT initiation. Background continuity improved in five patients and periodic discharge frequency decreased in six. There was a decrease in anesthetic use following the completion of ECT and an improvement in neurological exams. There were no associated adverse events. DISCUSSION: In our cohort, ECT was associated with improvement of ictal-interictal patterns on EEG, and resolution of SRSE, and was not associated with serious adverse events. Further controlled studies are needed.
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Epilepsia Resistente a Medicamentos , Eletroconvulsoterapia , Estado Epiléptico , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estado Epiléptico/terapia , Projetos de PesquisaRESUMO
Kohlschütter-Tönz syndrome (KTS) is a rare, autosomal recessive syndrome characterized by a triad of epilepsy, amelogenesis imperfecta and severe global developmental delay. It was first described in a Swiss family in 1974 by Alfried Kohlschütter and Otmar Tönz. It is caused by pathogenic variants in the ROGDI gene. To the best of our knowledge, there are currently 43 patients with a confirmed ROGDI gene pathogenic variant reported. Here, we review in detail the clinical manifestations of KTS, provide an overview of all reported genetically confirmed patients, and document an additional case of KTS-a 6-year-old Latvian girl-with a confirmed ROGDI gene pathogenic variant. In contrast to previous reports, we detected idiopathic bilateral nephrocalcinosis in this newly identified KTS patient. Perampanel proved an effective treatment for our patient with prolonged super-refractory status epilepticus. In order to better characterize this rare syndrome and its clinical course, it is important to report any additional symptoms and also the effectiveness of used therapies. Future research should focus on elucidating the mechanisms by which the absence/insufficiency of ROGDI-encoded protein causes the clinical manifestations of KTS. This knowledge could shape possible ways of influencing the disease's natural history with more effective therapies.
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Amelogênese Imperfeita , Epilepsia , Amelogênese Imperfeita/diagnóstico , Amelogênese Imperfeita/genética , Criança , Demência , Epilepsia/genética , Feminino , Humanos , Proteínas de Membrana/genética , Mutação , Proteínas Nucleares/genéticaRESUMO
BACKGROUND: The objective of this study was to evaluate the accuracy of seizure burden in patients with super-refractory status epilepticus (SRSE) by using quantitative electroencephalography (qEEG). METHODS: EEG recordings from 69 patients with SRSE (2009-2019) were reviewed and annotated for seizures by three groups of reviewers: two board-certified neurophysiologists using only raw EEG (gold standard), two neurocritical care providers with substantial experience in qEEG analysis (qEEG experts), and two inexperienced qEEG readers (qEEG novices) using only a qEEG trend panel. RESULTS: Raw EEG experts identified 35 (51%) patients with seizures, accounting for 2950 seizures (3,126 min). qEEG experts had a sensitivity of 93%, a specificity of 61%, a false positive rate of 6.5 per day, and good agreement (κ = 0.64) between both qEEG experts. qEEG novices had a sensitivity of 98.5%, a specificity of 13%, a false positive rate of 15 per day, and fair agreement (κ = 0.4) between both qEEG novices. Seizure burden was not different between the qEEG experts and the gold standard (3,257 vs. 3,126 min), whereas qEEG novices reported higher burden (6066 vs. 3126 min). CONCLUSIONS: Both qEEG experts and novices had a high sensitivity but a low specificity for seizure detection in patients with SRSE. qEEG could be a useful tool for qEEG experts to estimate seizure burden in patients with SRSE.
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Convulsões , Estado Epiléptico , Certificação , Coleta de Dados , Eletroencefalografia , Humanos , Convulsões/diagnóstico , Estado Epiléptico/diagnósticoRESUMO
How to cite this article: Dutta K, Satishchandra P, Borkotokey M. Medium-chain Triglyceride Ketogenic Diet as a Treatment Strategy for Adult Super-refractory Status Epilepticus. Indian J Crit Care Med 2022;26(1):139-140.
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OBJECTIVES: To describe the inpatient medical cost during hospitalization in children with status epilepticus (SE) and identify factors associated with the cost by a nationwide, multicenter study in China. MATERIALS & METHODS: We retrospectively identified pediatric inpatients with SE form Hospital Information System (HIS) of 44 hospitals in 27 provinces in China between 2013 and 2015. Inpatient medical cost and factors associated with the cost were analyzed. RESULTS: A total of 4041 children diagnosed with SE with inpatient medical cost were enrolled in the present study. The median age at admission was 2.9 (range 0.1-18) years, and 2271 patients were male (56.2%). The median inpatient medical cost of children with SE was $1175.5 (665.1-2320.6). The median inpatient medical cost was $3865.6 (1837.4-8210.4) in children with SRSE and $1048.6 (619.8-1865.4) in those with N-SRSE (pâ¯<â¯0.0001). Children with length of hospital stay (LOS)â¯>â¯7 showed a much higher inpatient medical cost than those with LOSâ¯≤â¯7â¯day ($2300.7 vs. $767.2, pâ¯<â¯0.0001). Regarding different etiologies, children with acute symptomatic etiology showed the highest median inpatient medical cost of $1681.1 (901.0-3699.6), in which children with central nervous system (CNS) infection reported $2606.0 (1380.0-5016.1) and prolonged febrile seizures (PFS) reported $909.8 (649.3-1322.0). Additionally, children with idiopathic/cryptogenic etiology reported a medical cost of $923.2 (548.9-1534.5). Multiple linear regression analysis of cost-driving factors revealed LOSâ¯>â¯7, examinations, treatment equipment and procedures, and treatment medicines were independently associated with a higher inpatient medical cost (R2â¯=â¯60.91). In addition, PFS and idiopathic/cryptogenic epilepsy etiology were independently associated with a lower cost. CONCLUSIONS: SE in children was a cost intensive disease in China with a median inpatient medical cost of $1175.5. LOS, etiology and examinations, treatment equipment and procedures, and treatment medicines were significantly associated with inpatient medical cost.
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Pacientes Internados , Estado Epiléptico , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Humanos , Lactente , Tempo de Internação , Masculino , Estudos Retrospectivos , Estado Epiléptico/epidemiologia , Estado Epiléptico/terapiaRESUMO
OBJECTIVE: Novel treatments are needed to control treatment-resistant status epilepticus (SE). We report a summary of clinical cases where perampanel was used in established SE, refractory SE (RSE), or super-refractory SE (SRSE). METHODS: Medical records were retrospectively reviewed for perampanel administration in SE at five European hospitals between 2011 and 2015. RESULTS: Of 1319 patients identified as experiencing SE, 52 (3.9%) received perampanel. Median latency from SE onset to perampanel initiation was 10 days. Patients with SE had previously failed benzodiazepines (when received) and a median of five other antiepileptic drugs (AEDs). Median initial perampanel dose was 6 mg/d, up-titrated to a median maximum dose of 10 mg/d. Perampanel was the last drug added in 32/52 (61.5%) patients, with response attributed to perampanel in 19/52 (36.5%) patients. A greater proportion of perampanel non-responders had SRSE (51.5%; 17/33) vs perampanel responders (31.6%; 6/19), and had failed a higher mean number of AEDs before initiating perampanel (5.9 vs 5.1, respectively). Most commonly reported adverse effects during perampanel treatment were dizziness (n = 1 [1.9%]) and somnolence (n = 1 [1.9%]). No serious adverse effects were documented, and none led to discontinuation of perampanel. CONCLUSIONS: Perampanel was administered to patients with established SE, RSE, or SRSE at greater initial doses than those administered in clinical practice to patients with epilepsy. The SE cases reported here represent a refractory and heterogeneous population, and rate of seizure cessation attributed to perampanel treatment (36.5%) represents a notable response. These data should be confirmed in a larger patient population.
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Anticonvulsivantes/uso terapêutico , Piridonas/uso terapêutico , Estado Epiléptico/tratamento farmacológico , Adulto , Áustria , Feminino , Finlândia , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Estudos Retrospectivos , Convulsões/prevenção & controle , Espanha , Resultado do TratamentoRESUMO
We convened an international group of experts to standardize definitions of New-Onset Refractory Status Epilepticus (NORSE), Febrile Infection-Related Epilepsy Syndrome (FIRES), and related conditions. This was done to enable improved communication for investigators, physicians, families, patients, and other caregivers. Consensus definitions were achieved via email messages, phone calls, an in-person consensus conference, and collaborative manuscript preparation. Panel members were from 8 countries and included adult and pediatric experts in epilepsy, electroencephalography (EEG), and neurocritical care. The proposed consensus definitions are as follows: NORSE is a clinical presentation, not a specific diagnosis, in a patient without active epilepsy or other preexisting relevant neurological disorder, with new onset of refractory status epilepticus without a clear acute or active structural, toxic or metabolic cause. FIRES is a subcategory of NORSE, applicable for all ages, that requires a prior febrile infection starting between 2 weeks and 24 hours prior to onset of refractory status epilepticus, with or without fever at onset of status epilepticus. Proposed consensus definitions are also provided for Infantile Hemiconvulsion-Hemiplegia and Epilepsy syndrome (IHHE) and for prolonged, refractory and super-refractory status epilepticus. This document has been endorsed by the Critical Care EEG Monitoring Research Consortium. We hope these consensus definitions will promote improved communication, permit multicenter research, and ultimately improve understanding and treatment of these conditions.
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Consenso , Epilepsia Resistente a Medicamentos/classificação , Síndromes Epilépticas/classificação , Estado Epiléptico/classificação , Epilepsia Resistente a Medicamentos/diagnóstico , Síndromes Epilépticas/diagnóstico , Humanos , Estado Epiléptico/diagnósticoRESUMO
BACKGROUND: Management of refractory status epilepticus (SE) commonly involves the induction of burst suppression using intravenous anesthetic agents. However, the endpoints of these therapies are not well defined. Weaning anesthetic agents are complicated by the emergence of electroencephalogram (EEG) patterns along the ictal-interictal continuum (IIC), which have uncertain significance given that IIC patterns may worsen cerebral metabolism and oxygenation, have a dissociation between scalp and depth EEG recordings, or may indicate a late stage of SE itself. Determining the significance of IIC patterns in the unique context of anesthetic weaning is important to prevent the potential for unnecessarily prolonging anesthetic coma. METHODS: Among 118 individuals with SE, we retrospectively identified a series of patients who underwent at least 24 h of burst-suppression therapy, experienced two or more weaning trials, and developed IIC patterns during anesthetic weaning. Anesthetic titration strategies during the emergence of these patterns were examined. RESULTS: Each of the six individuals who met inclusion criteria experienced aggressive weaning despite the emergence of IIC patterns. The IIC patterns that were encountered during anesthetic weaning (including generalized and lateralized periodic discharges) are described in detail. Favorable outcomes were reported in each subject. CONCLUSION: IIC patterns encountered during anesthetic weaning may be transitional and warrant observation, allowing for the emergence of more definitive clinical or electrographic results. The metabolic impact of these IIC patterns on brain activity is uncertain, but weaning strategies that treat IIC as a surrogate of recurrent SE risk further prolonging anesthetic management and its known toxicity. We speculate that these patterns may have a context-specific association with SE relapse, with less-risk conferred when these patterns are observed during the weaning of anesthetic agents after prolonged burst-suppression therapy. Other electrographic features aside from this clinical context may discriminate the risk of SE relapse, such as EEG background activity.
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Anestésicos Intravenosos/administração & dosagem , Cuidados Críticos/métodos , Avaliação de Processos e Resultados em Cuidados de Saúde , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Functional neurologic outcome for children with refractory and super-refractory status epilepticus has not been well defined. METHODS: Retrospective chart review including children age 0-17 years who received pentobarbital infusion from 2003 to 2016 for status epilepticus. Outcomes were defined in terms of mortality, need for new medical technology assistance at hospital discharge and functional neurologic outcome determined by pediatric cerebral performance category score (PCPC). Potential patient characteristics associated with functional neurologic outcome including age, sex, ethnicity, etiology of the status epilepticus, and duration of pentobarbital infusion were evaluated. RESULTS: Forty children met inclusion criteria. In-hospital mortality was 30% (12/40). Of survivors, 21% (6/28) returned to baseline PCPC while half (14/28) declined in function ≥ 2 PCPC categories at hospital discharge. 25% (7/28) of survivors required tracheostomy and 27% (7/26) required new gastrostomy. Seizures persisted at discharge for most patients with new onset status epilepticus while the majority of patients with known epilepsy returned to baseline seizure frequency. Etiology (p = 0.015), PCPC at admission (p = 0.0006), new tracheostomy (p = 0.012), and new gastrostomy tube (p = 0.012) were associated with increase in PCPC score ≥ 2 categories in univariable analysis. Duration of pentobarbital infusion (p = 0.005) and length of hospital stay (p = 0.056) were longer in patients who demonstrated significant decline in neurologic function. None of these variables maintained statistical significance when multiple logistic regression model adjusting for PCPC score at admission was applied. At long-term follow-up, 36% (8/22) of children demonstrated improvement in PCPC compared to discharge and 23% (5/22) showed deterioration including three additional deaths. CONCLUSIONS: Mortality in this population was high. The majority of children experienced some degree of disability at discharge. Despite prolonged pentobarbital infusion, there were cases of survival with good neurologic outcome.
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Epilepsia Resistente a Medicamentos/tratamento farmacológico , Moduladores GABAérgicos/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Pentobarbital/farmacologia , Estado Epiléptico/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Epilepsia Resistente a Medicamentos/mortalidade , Epilepsia Resistente a Medicamentos/cirurgia , Feminino , Seguimentos , Moduladores GABAérgicos/administração & dosagem , Mortalidade Hospitalar , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Masculino , Pentobarbital/administração & dosagem , Estudos Retrospectivos , Estado Epiléptico/mortalidade , Estado Epiléptico/patologia , Estado Epiléptico/cirurgiaRESUMO
OBJECTIVE: Super-refractory status epilepticus (SRSE) is a severe condition in which a patient in status epilepticus (SE) for ≥24 h does not respond to first-, second-, or third-line therapy. The economic impact of SRSE treatment remains unclear. A health insurance research database was used for a population-based estimation of SRSE-associated inpatient costs, length of stay, and mortality in Germany. METHODS: An algorithm using International Classification of Diseases, 10th Edition coding and treatment parameters identified and classified patients in a German statutory health insurance database covering admissions from 2008 to 2013 as having refractory SE (RSE) or SRSE. Admissions data in our study refer to these classifications. Associated patient data included costs, procedures, and demographics. RESULTS: The algorithm identified 2,585 (all type) SE admissions, classified as 1,655 nonrefractory SE (64%), 592 (22.9%) RSE, and 338 (13.1%) SRSE, producing database incidence rates of 15.0 in 100,000, 5.2 in 100,000, and 3.0 in 100,000 per year, respectively. Median cost per admission was 4,063 for nonrefractory SE, 4,581 (p < 0.001) for RSE, and 32,706 (p < 0.001) for SRSE. Median length of stay varied significantly between 8 days (mean = 13.6) in nonrefractory SE, 14 days in RSE, and up to 37 days in SRSE. Discharge mortality increased from 9.6% in nonrefractory SE to 15.0% (p < 0.001) in RSE and 39.9% (p < 0.001) in SRSE. SIGNIFICANCE: This study evaluated the hospital treatment costs associated with admissions classified by the algorithm as SRSE in Germany. SRSE represented 13% of all SE admissions, but resulted in 56% of all SE-related costs. The lack of approved treatments and limited number of evidence-based treatment guidelines highlight the need for further evaluations of the SRSE burden of illness and the potential for further optimization of treatments for SRSE.
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Custos de Cuidados de Saúde/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Estado Epiléptico/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha/epidemiologia , Humanos , Tempo de Internação/economia , Masculino , Pessoa de Meia-Idade , Estado Epiléptico/mortalidade , Estado Epiléptico/terapia , Falha de TratamentoRESUMO
OBJECTIVE: Febrile infection-related epilepsy syndrome (FIRES) is a catastrophic epileptic encephalopathy described as explosive onset of super refractory status epilepticus (SRSE) in previously healthy children. We describe electroencephalography (EEG) abnormalities in the hyperacute phase of FIRES, with the aim of contributing to the diagnostic characterization of a syndrome otherwise lacking specific biomarkers. METHODS: This is a retrospective single-center, case series of seven children with FIRES. Cases were identified from a Neurocritical Care database. Patient characteristics and clinical course were obtained from electronic medical records. Electroencephalography recordings were reviewed in two segments: the initial 12 h of recording and the 12 h prior to initiation of a medically induced burst suppression (BS). RESULTS: Fourteen 12-h segments of video-electroencephalography (EEG) recordings were analyzed for commonalities. A beta-delta complex resembling extreme delta brush (EDB) occurred in at least one 12-h segment for all patients. In six patients, seizures were brief and relatively infrequent during the first recording, with a gradual evolution to status epilepticus by the second. We observed a characteristic electrographic seizure pattern in six of seven patients with prolonged focal fast activity at onset. Shifting seizures were seen in four of seven patients. SIGNIFICANCE: The diagnosis of FIRES is typically assigned late in a patient's clinical course, which has broad implications for clinical care and research. We retrospectively analyzed acute EEG features in seven patients with FIRES and discovered three common features: gradual increase in seizure burden, presence of a recurrent EDB, and a typical seizure pattern. Recognition of this pattern may facilitate early diagnosis and treatment.
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Encefalopatia Aguda Febril/complicações , Ritmo Delta/fisiologia , Epilepsia/complicações , Encefalopatia Aguda Febril/fisiopatologia , Adolescente , Criança , Pré-Escolar , Eletroencefalografia , Epilepsia/fisiopatologia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Tempo , Gravação em VídeoRESUMO
BACKGROUND: The aim was to determine predictors of hospital and 1-year mortality in patients with intensive care unit (ICU)-treated refractory status epilepticus (RSE) in a population-based study. METHODS: This was a retrospective study of the Finnish Intensive Care Consortium (FICC) database of adult patients (16 years of age or older) with ICU-treated RSE in Finland during a 3-year period (2010-2012). The database consists of admissions to all 20 Finnish hospitals treating RSE in the ICU. All five university hospitals and 11 out of 15 central hospitals participated in the present study. The total adult referral population in the study hospitals was 3.92 million, representing 91% of the adult population of Finland. Patients whose condition had a post-anoxic aetiological basis were excluded. RESULTS: We identified 395 patients with ICU-treated RSE, corresponding to an annual incidence of 3.4/100,000 (95% confidence interval (CI) 3.04-3.71). Hospital mortality was 7.4% (95% CI 0-16.9%), and 1-year mortality was 25.4% (95% CI 21.2-29.8%). Mortality at hospital discharge was associated with severity of organ dysfunction. Mortality at 1 year was associated with older age (adjusted odds ratio (aOR) 1.033, 95% CI 1.104-1.051, p = 0.001), sequential organ failure assessment (SOFA) score (aOR 1.156, CI 1.051-1.271, p = 0.003), super-refractory status epilepticus (SRSE) (aOR 2.215, 95% CI 1.20-3.84, p = 0.010) and dependence in activities of daily living (ADL) (aOR 2.553, 95% CI 1.537-4.243, p < 0.0001). CONCLUSIONS: Despite low hospital mortality, 25% of ICU-treated RSE patients die within a year. Super-refractoriness, dependence in ADL functions, severity of organ dysfunction at ICU admission and older age predict long-term mortality. TRIAL REGISTRATION: Retrospective registry study; no interventions on human participants.
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Unidades de Terapia Intensiva/estatística & dados numéricos , Mortalidade , Estado Epiléptico/mortalidade , Fatores de Tempo , Adulto , Idoso , Distribuição de Qui-Quadrado , Estudos de Coortes , Feminino , Finlândia , Humanos , Incidência , Unidades de Terapia Intensiva/organização & administração , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Estatísticas não ParamétricasRESUMO
Super refractory status epilepticus (SRSE) is a life-threatening condition in which seizures do not respond to third-line anticonvulsant drug therapy. SRSE is associated with high mortality. How often SRSE occurs, what are the risk factors leading to this condition, and what is the effect on clinical outcome of failure to control seizures are poorly defined. Several studies have evaluated magnetic resonance imaging (MRI) findings in status epilepticus (SE), confirming that SE may directly cause selective neuronal necrosis due to excitotoxic mechanisms, as described in clinical case reports and experimental models. The aim of our study is to illustrate, in a case of SRSE, MRI signal changes during time and to describe which cerebral structures are early involved in this difficult clinical condition. We investigated with serial MRI study a patient affected by childhood generalized epilepsy who developed SRSE of unknown etiology during adulthood. MRI scans showed brain signal changes according to progressive electro-clinical worsening, particularly an early involvement of striatum/pallidus. An extended literature exists about transient MRI changes in SE, but not enough about SRSE, because of the difficulties in executing serial MRI studies in patients with such risky condition. MRI findings in SRSE must be investigated with particular care in order to detect early changes in basal ganglia that could suggest severe prognosis.
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Corpo Estriado/diagnóstico por imagem , Globo Pálido/diagnóstico por imagem , Imageamento por Ressonância Magnética , Estado Epiléptico/diagnóstico por imagem , Estado Epiléptico/patologia , Adulto , Ondas Encefálicas/fisiologia , Eletroencefalografia , Humanos , Processamento de Imagem Assistida por Computador , MasculinoRESUMO
BACKGROUND: Super-refractory status epilepticus (SRSE) ensues when there is no improvement of seizure control in response to anesthetic therapy or seizure recurrence after reduction of anesthetic agents. There is no consensus on standard of care for SRSE. Ketogenic diet (KD) has reported success, but technical challenges exist including inability to feed patients, concomitant steroid use, acidotic states, and lack of dieticians with experience. The optimal protocol for KD is yet to be determined. We describe our approach to initiation of KD in the pediatric intensive care unit (PICU). METHODS: Patients with SRSE who had KD initiation in the PICU were identified. Data from the hospital course were supplemented by review of the electronic medical record. RESULTS: Nine children with SRSE who had KD initiated in the PICU were identified. Descriptive analysis was performed. Mean age was 5.4 years (SD 2.24). Median number of days to start KD from detection of seizures was 13 [interquartile range (IQR) 10-16]. Mean time to achieve ketosis was 4.2 days (SD 3.4). The median number of antiepileptic drugs (AEDs) trialed before KD was started was 4 [IQR 3-4], and the median number of continuous infusions was 2 [IQR 2-3]. After initiation of KD, most patients were weaned off anesthetic infusions by 1 week. Outcomes were variable. CONCLUSIONS: We demonstrated the feasibility of a practical approach to initiation of KD for children with SRSE. These children were successfully weaned off continuous anesthetic infusions. Larger studies are needed to determine effectiveness, safety, and tolerability of KD in the management of SRSE as well as ease of implementation.
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Dieta Cetogênica/métodos , Epilepsia Resistente a Medicamentos/dietoterapia , Unidades de Terapia Intensiva Pediátrica , Avaliação de Resultados em Cuidados de Saúde , Estado Epiléptico/dietoterapia , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Humanos , MasculinoRESUMO
OBJECTIVE: This study aims to determine the general frequency, mortality, and risk factors of super-refractory status epilepticus (SRSE) versus non-refractory status epilepticus (NRSE) and refractory status epilepticus (RSE). METHODS: This work is a retrospective study. Clinical data of patients who were diagnosed with status epilepticus (SE) in the neurological ward and neuro-intensive care unit of West China Hospital from January 2009 to December 2012 were collected and analyzed. RESULTS: A total of 98 patients were included in the study. The percentages of NRSE, RSE, and SRSE were 67.3%, 20.4%, and 12.2%, respectively. Convulsive SE was the main seizure type among the three groups. The most common cause of NRSE was related to epilepsy (EP). However, 67.7% of SRSE cases were caused by acute encephalitis. Moreover, 47% of SE and 40% of RSE cases had a history of EP, whereas only 8.3% of SRSE cases had such history (P < 0.01). The percentage of patients with STESS ≤2 was lowest in the SRSE group without statistical significance (P > 0.05). The general mortality of SE was 7.1%, whereas that of SRSE was 50%. During follow-up, most SRSE patients who survived have developed symptomatic EP. CONCLUSIONS: This study was the first to use the statistical percentage of SRSE. Approximately 12.2% of SE cases will result in SRSE, which is a challenging medical situation for doctors. Patients with first episodes and acute encephalitis were also prone to develop SRSE.
Assuntos
Estado Epiléptico/epidemiologia , Estado Epiléptico/etiologia , China/epidemiologia , Humanos , Estudos Retrospectivos , Fatores de Risco , Convulsões/epidemiologia , Convulsões/etiologiaRESUMO
There remains a need for more efficacious treatments for status epilepticus. Prolonged seizures result in the release of ATP from cells which activates the P2 class of ionotropic and metabotropic purinoceptors. The P2X receptors gate depolarizing sodium and calcium entry and are expressed by both neurons and glia throughout the brain, and a number of subtypes are upregulated after status epilepticus. Recent studies have explored the in vivo effects of targeting ATP-gated P2X receptors in preclinical models of status epilepticus, with particular focus on the P2X7 receptor (P2X7R). The P2X7R mediates microglial activation and the release of the proepileptogenic inflammatory cytokine interleukin 1ß. The receptor may also directly modulate neurotransmission and gliotransmission and promote the recruitment of immune cells into brain parenchyma. Data from our group and collaborators show that status epilepticus produced by intraamygdala microinjection of kainic acid increases P2X7R expression in the hippocampus and neocortex of mice. Antagonism of the P2X7R in the model reduced seizure severity, microglial activation and interleukin 1ß release, and neuronal injury. Coadministration of a P2X7R antagonist with a benzodiazepine also provided seizure suppression in a model of drug-refractory status epilepticus when either treatment alone was minimally effective. More recently, we showed that status epilepticus in immature rats is also reduced by P2X7R antagonism. Together, these findings suggest that P2X receptors may be novel targets for seizure control and interruption of neuroinflammation after status epilepticus. This article is part of a Special Issue entitled "Status Epilepticus".
Assuntos
Hipocampo/metabolismo , Inflamação/metabolismo , Antagonistas do Receptor Purinérgico P2X/uso terapêutico , Receptores Purinérgicos P2X/metabolismo , Estado Epiléptico/metabolismo , Animais , Hipocampo/efeitos dos fármacos , Inflamação/tratamento farmacológico , Masculino , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Antagonistas do Receptor Purinérgico P2X/farmacologia , Ratos , Estado Epiléptico/tratamento farmacológico , Resultado do TratamentoRESUMO
Refractory status epilepticus (RSE) is a particular critical condition characterized by seizures that continue despite the use of first- and second-line therapies and by high mortality. To date, only one prospective study investigated clinical features and prognostic factors in RSE. In this study, we performed a one-year prospective survey to identify clinical features, outcomes, and variables associated with the development of RSE in the adolescent and adult population of Modena, northern Italy. We observed 83 episodes of SE in 83 patients. In 31% of the cases, third-line therapy (anesthetic drug) was needed. Among this group, 14% resolved and were classified as RSE, while, in 17%, seizures recurred at withdrawal of anesthetics and were classified as super-RSE. The development of RSE/super-RSE was associated with a stuporous/comatose state at presentation and with the absence of a previous history of epilepsy. Refractory status epilepticus/super-refractory status epilepticus showed a worse outcome compared with responsive SE: 54% versus 21% for 30-day mortality; 19% versus 56% for a return to baseline condition. This prospective study confirms stupor/coma at onset as a relevant clinical factor associated with SE refractoriness. We observed a rate of RSE comparable with previous reports, with high mortality and morbidity. Mortality in the observed RSE was higher than in previous studies; this result is probably related to the low rate of a previous epilepsy history in our population that reflects a high incidence of acute symptomatic etiologies, especially the inclusion of patients with postanoxic SE who have a bad prognosis per se. This article is part of a Special Issue entitled "Status Epilepticus".